Prenatal development of the intrinsic nerves of the muscles of the human foot

Myelogenesis and blood supply of the intraorganic nerves have been studied in 4-6- and 7-9-month-old human fetuses. At first, the intramuscular nerves are presented as very thick fasciculi (the diameter is more than 90), thick (the diameter is from 50 up to 90) and single muddle neural fasciculi (the diameter is from 30 up to 50 mcm). The microcirculatory blood bed is formed at the expense of branches of the blood vessel-satellites and the blood vessels of the surrounding tissues and is carried out, without any interruption, along the whole extent. In 7-9-month-old fetuses the neural apparatus becomes more complex. The number of the middle neural fasciculi appear. On the background of fine neural fibers in the fasciculi a small part of the middle neural fibers appears, and in the musculus flexor digitorum brevis--single thick neural fibers. The intramuscular nerves have their own hemocirculatory bed presented by microvessels that are on the perineurium surface, in its bulck and among neural fibers.     

The intraorganic lymphatic bed of the mucous membrane of the tongue

The intraorganic lymphatic bed of the canine tongue mucous membrane is presented by the superficial and deep capillary networks and by the plexuses of the intraorganic lymphatic vessels. The capillaries of the superficial network in the thickness of the mucous membrane of the dorsal surface of the lingual tip, body and root form the lymphatic bed of the mechanical and gustatory papillas. The diameter of the capillaries in the both networks and in the intraorganic lymphatic vessels is greater in the mucous membrane of the ventral surface of the tip and of the lateral surfaces of the lingual body, and density of their arrangement is higher in the mucous membrane on the dorsal surface of the lingual tip, body and root. The capillaries of the superficial network in all areas of the lingual mucous membrane are thinner than those of the deep network, and the loops formed by the capillaries of the superficial network are less than the loops of the deep network.     

Structural features of the intrinsic venous bed of the human urinary bladder

The intraorganic veins of the human urinary bladder have been studied in a vast sectional material. The veins within the organ make an enormous multilayered plexus which is differently organized in various layers of its wall. Abundant anastomoses, multiplicated ways for outflow from every layer, manifested interactions between the venous plexuses are specific for the intraorganic venous bed of the urinary bladder. The structures for an active regulating the hemomicrocirculatory blood stream are widely presented in the urinary bladder. In its every tunic certain specific morpho-functional features for organization and adaptation of the intraorganic venous bed are revealed.     

Development of the neural apparatus of the human pancreas in prenatal ontogeny

In human embryos, prefetuses and fetuses from 6 to 40 weeks of development 82 preparations of the pancreas have been studied; 39 series of slices of the human embryos have been impregnated after Bielschowsky-Boeke. For the first time the nerves grow into the pancreas anlage in embryos of 16 mm long (6 weeks). The main sources supplying the pancreas with the nerves in the period studied are nervus vagus, celiac, hepatic, splenic, right adrenal, superior mesenteric and intermesenteric plexuses. Three stages in formation of the innervational apparatus of the pancreas are distinguished during the intrauterine development. The first stage is characterized by beginning of the nerve growing into the pancreas anlage. For the second stage an increased development of the intraorganic innervational apparatus and appearance of the all main sources of the organ's innervation are specific. The third stage is characterized with an increased differentiation of receptor zones in various parts of the pancreas. The development of the pancreatic innervational apparatus by the time of birth is not completed.     

Age-related dynamics of blood supply and vascular-tissue interrelations in the human pineal body

Thirty-seven pineal bodies have been studied. They have been obtained from persons of both sex at the age of 18 up to 88 years, perished from accidental causes. Specific volumes of the epiphyseal tissues and vascular constructions of all types have been determined in histological preparations. In young age (up to 40-45 years) the volume of the intraorganic epiphyseal vascular bed is greater, and its blood supply is better than in persons of elderly and old age, when the sclerosing process in the organ occurs at the expense of outgrowth of fibrous elements of the connective tissue carcass. During the pineal body involution, the volume of its intraorganic vascular bed decreases essentially. This results in certain disturbances of blood supply and affects functional activity of the organ.     

Development of the hemomicrocirculatory bed of the human gonads during the prenatal period of ontogeny

The formation of the organospecific hemomicrocirculatory bed of the ovaries and testes has been studied by a complex of light, transmissive and scanning electron microscopy in 3--9-month-old human fetuses. The change of the diffusive protocapillary bed is secured by: 1) reduction of some protocapillaries; 2) appearance of secondary capillaries from the growth buds of the preceeding microvessels; 3) formation of arteriolar and venular links of the hemomicrocirculatory bed from the protocapillaries at the expense of differentiation of the developing paravasal connective tissue into cellular elements of the muscular and adventitial tunics. The secondary blood capillaries of the human gonads are predominantly formed intraendothelially. During the prenatal ontogenesis presence of the secondary blood capillaries of somatic uninterrupted type is specific for the human gonads.     

Formation of primary microvessels in the early stages of prenatal human morphogenesis

By means of light and electron microscopy, the most general mechanisms of formation and development of primary blood microvessels in functionally different organs (adenohypophysis, thyroid, thymus, liver, spleen, small and large intestine) have been studied in human embryos 4-8 weeks of age. Ultrastructure of cells in the extra- and intraorganic mesenchyme is described; to the latter belongs the leading role in organization the pathways of the prevascular microcirculation. The primary microvessels are formed as a result of canalization of the intercellular clefts, lining with mesenchymal cells, that gradually transfer into primordial endotheliocytes. Basing on ultrastructural analysis, certain stages of differentiation of protocapillary endotheliocytes have been defined and described in different organs. The change of the prevascular microcirculation into the intraorganic protocapillary bed (the primary blood bed) is an essential and necessary stage of the organogenesis.     

Blood vessels of the hypophysis]

The construction of the intraorganic vessels of the hypophysis was studied by different injectional methods in cats and partly in dogs. The obtained data confirmed the portal microcirculation in the hypophysis of the animals under investigation. Anatomical and some experimental data speak in favour of the blood flow direction in the portal system from the medial eminence towards the anterior part of the adenohypophysis. The capillaries of the portal system were demonstrated to anastomose with arcuate nucleus of the hypothalamus and with the caudal parts of the neurohypophysis. The experiments with intravital accumulation of the trypan blue revealed macrophagal activity of the perivascular connective tissue elements of the portal system. An attempt was made to objectively analyze the capillary architectonics of the hypophysis portal system. The obtained data on its peculiar features are discussed in connection with the capillary construction and peculiarities of the metabolism of the hypothalmic neurosecretory nuclei.     

Age and changes in the structure of the walls of the intrinsic arteries of the uterus

By means of common histological, histochemical and morphometrical methods age changes in the cushion-like intimal protrusions of the intraorganic arteries have been studied in 176 uteri of women at all ages that died from trauma and other diseases which do not produce any changes in the uterus. Beginning from two years of age, in the uterus segmentary artery wall certain intimal thickenings are revealed; at this age they consist of immature fibrillar and cellular elements of the connective tissue and single myocytes. At the pubertal age an intensive development of the cushion-like protrusions is observed. The amount of myocytes in them increases at the expense of migration from muscular tunic of the vessel; they arrange chaotically. Then the structure of the elastic and collagenous carcass of the protrusions becomes more complex, the myocytes in them are oriented along the course of the artery, or along the sloping spiral. During adolescence and mature age, cyclic changes in the wall structure of the uterus intraorganic arteries are observed, depending on the phase of the menstrual cycle. During the second part of the proliferative phase, certain retruction of the protrusions is observed, and at the end of the secretion phase--maximal increase in their height. The intimal protrusions are specialized structures, playing an important role in ensuring an optimal blood circulation in the uterus during ovulation and in performing menstruation. Reverse development of these structures takes place in elderly and old age.     

Effect of ultrasound of high intensity on the intraorganic vessels of the liver]

Under study was the influence of a single 3-minute-long exposure to ultrasound of high intensity (2 wt/cm2) upon intraorganic vessels of the liver in albino rats. The circulatory bed was examined 10 min., 5, 15 and 30 days after treatment with ultrasound. Methods ox injection, rentgenography, claering and histology revealed an unfavourable effect of ultrasound causing local construction of arteries and veins in early terms, uneven filling of the capillary bed with the injected mass, dilatation and deformity of capillaries. The above changes grew more pronounced during 15 days, by the end of the month they diminished but not disappeared.     

Circulatory system in chicken skeletal muscle in the second half of embryogenesis: Shape,blood flow,and vascular reactivity

A restructuring of the capillary bed—from the embryonic structure with a three-dimensional network of wide and long protocapillaries to the mature structure with high density of thin and short capillaries along the fibers—has been demonstrated in the chick skeletal muscle on embryonic days 10–19 by morphometric analysis. In this case, the specific blood flow and capillary luminal area per cm³ of the muscle remained unaltered, while the blood volume in it significantly dropped. The response of muscle circulation to nitroprusside (increase) and noradrenaline (decrease) appeared in 19-day-old embryos, but this response could develop only under conditions of initially low or high blood flow, respectively. We propose that the arterial trunk lumen area to the total capillary lumen area remains constant as the intraorganic circulation is formed, which provides for the required linear blood velocity in capillaries.     

Structural changes in the pulmonary vessels and parenchyma in experimental hypercholesterolemia and atherosclerosis

Light and electron microscopy were employed to study the microcirculatory bed (MCB), intraorganic vessels and lung tissue in rabbits in the first hours (1, 3, 6, 15, 24 and 48 h) after a single administration of cholesterol (ChS) and in the course of the development of experimental atherosclerosis. The MCB demonstrated changes such as dilatation of the venular part, arteriolar constriction, red cell aggregation in capillaries and venules, and stases. At the early stages of experimental atherosclerosis induced by the diet the permeability of the air-blood barrier and the synthesis of lung surfactant were found to be deranged. Vessel-tissue changes in the lungs progressed with an increase in the length of the diet (1-8 months) and were alike the picture seen in chronic nonspecific lung diseases, particularly in what is called senile emphysema. A relationship was established between the degree of changes in the MCB and HCh gravity. Atherosclerotic lesions in the intraorganic arteries occur and progress parallel with the development of this process in the intramural arteries of the myocardium. The data obtained attest to an important role of lipid metabolism disorders in the development of lung pathology and may have a certain significance in specifying the pathogenesis of chronic nonspecific lung diseases, especially.     

New findings on the innervation of nerves proper]

The study by the author and his co-workers of the innervation of the sheaths of extraorganic (spinal and cerebral) and intraorganic nerves has shown that their nervous apparatus is differentiated in accordance with differentiation of epi-, peri- and endoneurium. The peculiar features of the innervation of sheaths of different nerves correspond to their functions and pathoplastical individuality and manifest themselves by uneven complexity, concentration and microtopography of nerve structures in the sheaths and by distinctions in the development and reactivity. Interrelationships and correlation was established between the specific functional readiness of nerve conductors and the structural organization of their sheaths' nervous apparatus. The phenomenon of reciprocal innervation of nerves was established in experiment as well as earlier reactive and compensatory-reparative processes in the nervous apparatus of nerve sheaths as compared with their conductors.     

Age-related characteristics of the structure of renal arteries

The investigation has been performed on 337 preparations of human kidneys and on 129 clinical angiograms of kidneys at different age without renal and cardiovascular system pathology. A complex of morphological techniques, mathematical method including, has been used. Peculiarities in architectonics of the intraorganic renal arterial vessels have been described during various age periods of postnatal ontogenesis; essential variations of the renal artery index have been revealed in newborns and adolescents. They reflect functional rearrangement of the vessels during these age periods. Six periods in formation of the renal arterial intraorganic vessels have been determined, when probability of decrease and failure of their compensatory potentialities is especially great.     

Innervation of the renal vasculature of the toad (Bufo marinus)

The innervation of the dorsal aorta and renal vasculature in the toad (Bufo marinus) has been studied with both fluorescence and ultrastructural histochemistry. The innervation consists primarily of a dense plexus of adrenergic nerves associated with all levels of the preglomerular vasculature. Non-adrenergic nerves are occasionally found in the renal artery, and even more rarely near the afferent arterioles. Many of the adrenergic nerve profiles in the dorsal aorta and renal vasculature are distinguished by high proportions of chromaffin-negative, large, filled vesicles. Close neuromuscular contacts are common in both the renal arteries and afferent arterioles. Possibly every smooth muscle cell in the afferent arterioles is multiply innervated. The glomerular capillaries and peritubular vessels are not innervated, and only 3-5% of efferent arterioles are accompanied by single adrenergic nerve fibres. Thus, nervous control of glomerular blood flow must be exerted primarily by adrenergic nerves acting on the preglomerular vasculature. The adrenergic innervation of the renal portal veins and efferent renal veins may play a role in regulating peritubular blood flow. In addition, glomerular and postglomerular control of renal blood flow could be achieved by circulating agents acting via contractile elements in the glomerular mesangial cells, and in the endothelial cells and pericytes of the efferent arterioles. Some adrenergic nerve profiles near afferent arterioles are as close as 70 nm to distal tubule cells, indicating that tubular function may be directly controlled by adrenergic nerves.     

Intraorganic lymphatic bed of the cattle heart

Lymphomicrocirculatory networks of endocardium, myocardium and epicardium, as well as lymphatic vessels of four orders represent the intraorganic lymphatic bed of the cattle heart. In the endocardium there is a lymphatic network with close loops and a small amount of blindly beginning capillaries. The capillary lymphatic bed of the endocardial trabeculae carneae is much more dense than that in the other part of the endocardial surface. The spatial lymphatic network of the myocardium is joined with the lymphomicrocirculatory networks of the endocardium and epicardium by means of a large amount of connections. The epicardial lymphatic bed is formed by blindly beginning lymphatic capillaries, which situate in close and nonclose loops of the lymphatic network. In the epicardium there is only one lymphatic network. The size of the loops and the diameter of the lymphatic capillaries is directly proportional to the age of the animals.     

Intrinsic nerves of the pectoralis major and minor in man

In the human intraorganic nerves of the thoracic muscles amyelin fibers make 62% and myelin ones--38%. In transversal sections ultrastructure of the myelin and amyelin fibers varying in their diameters has been studied. In the myelin and amyelin fibers the amount of various organells is not equal: in the amyelin fibers the arrangement density of microtubules is greater than that of neurofilaments, there is a reverse dependence between the amount of the microtubules and the neurofilaments on the one hand, and the fibrilar diameter, on the other hand. In the myelin fibers with the increasing diameter, the amount of the neurofilaments increases, while that of the microtubules decreases.     

Combination of vasostatin gene therapy with cyclophosphamide inhibits growth of B16(F10) melanoma tumours

Angiogenesis, i.e. formation of new blood vessels out of pre-existing capillaries, is essential to the development of tumour vasculature. The discovery of specific antiangiogenic inhibitors has important therapeutic implications for the development of novel cancer treatments. Vasostatin, the N-terminal domain of calreticulin, is a potent endogenous inhibitor of angiogenesis and tumour growth. In our study, using B16(F10) murine melanoma model and electroporation we attempted intramuscular transfer of human vasostatin gene. The gene therapy was combined with antiangiogenic drug dosing schedule of a known chemotherapeutic (cyclophosphamide). The combination of vasostatin gene therapy and cyclophosphamide administration improved therapeutic effects in melanoma tumours. We observed both significant inhibition of tumour growth and extended survival of treated mice. To our knowledge, this is one of the first reports showing antitumour efficacy of electroporation-mediated vasostatin gene therapy combined with antiangiogenic chemotherapy.     

Localized agglutinin staining in muscle capillaries from normal and very old atrophic human muscle using winged bean (Psophocarpus tetragonolobus) lectin

 The winged bean (Psophocarpus tetragonolobus) agglutinin (total lectin) and its basic (WBA I) and acidic isoform (WBA II) were used to analyze capillaries in sections from human muscle. The microvessels were clearly labeled after incubation with the lectins in both normal muscle and in old muscles with age-related type II atrophy or muscle fiber grouping. Muscle fibers, nerves, and connective tissue remained unstained. The total lectin detected muscle capillaries from all blood group AB0 individuals. The isoform WBA I reacted only with blood vessels in blood group A and B individuals, while the blood vessels in blood group 0 individuals were demonstrated with WBA II. WBA I staining was inhibited by p-nitrophenyl α-galactopyranoside and N-acetylgalactosamine, whereas 2′-fucosyllactose and preincubation with an antibody against type-1 chain H abolished capillary staining with WBA II. The study demonstrates the usefulness of WBA as a marker of capillaries in human muscle. Accepted: 2 September 1996     

Hypertrophic smooth muscle

Summary In adult guinea-pigs, oral to a partial obstruction to the flow of ingesta in the ileum there is a marked increase in the diameter of the intestine and a hypertrophy of the muscle coat. The features of the intramuscular blood vessels and of the extracellular materials were studied by electron microscopy. There is a small increase in the amount of intercellular space measured morphometrically. The basal lamina surrounding the hypertrophic muscle cells is more prominent than in controls. In the intercellular space between muscle cells, in addition to collagen fibrils, there is abundant amorphous material of medium electron density and streak-like, electron-dense material often similar to thickened basal laminae. The total amount of stroma (intercellular materials) present in a unit length of intestine is greatly increased in hypertrophy; a role of the muscle cells in the production of new collagen and other extracellular elements is suggested by the present observations. Many new intramuscular blood vessels (mainly capillaries, some of which are fenestrated) are formed during hypertrophy of the intestinal wall, so that the circular muscle layer remains as well vascularized in the hypertrophic intestine as in the controls. Blood vessels are not formed within the longitudinal muscle layer.